We wish to relate the detailed structure of key fibrous protein assemblies to their functional roles in the cell. Muscle is a major focus for analysis. X-ray diffraction and electron microscopic studies are being carried out on the tropomyosin-troponin complex, which is the regulatory switch on the thin filaments in muscle; and on molluscan myosin, where the regulatory switch is associated with the enzymic portion or "head" of the molecule. The proteins are being examined in the isolated states, in crystalline arrays and in whole muscle. We are attempting to define the precise architecture of myosin filaments in a wide variety of muscles. Analysis is underway to obtain a high resolution structure for hydrated microtubules, and on the possible role of nerve growth factor a specific morphogen of the cytoskeleton. A further goal of this project is the X-ray crystallographic study of modified fibrinogen, to obtain a low resolution image of the molecule, and to identify its interactions in the assembly of the fibrin clot.